ArticleFrontiers in physiology2015
In adenosine A2B knockouts acute treatment with inorganic nitrate improves glucose disposal, oxidative stress, and AMPK signaling in the liver.
Article in Frontiers in physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 46 citations in OpenAlex.
- Hormetic association between sodium nitrate and liver enzymes: a study in female and male rats.Toxicology research · 2025Article
- Protective effects of long-term nitrate administration against ovariectomy-induced kidney dysfunction in rats.Pharmacological reports : PR · 2023Article
- Anti-oxidant effect of nitrite in the pancreatic islets of type 2 diabetic male rats.Iranian journal of basic medical sciences · 2023Article
- Preliminary Evidence of the Potent and Selective Adenosine A2B Receptor Antagonist PSB-603 in Reducing Obesity and Some of Its Associated Metabolic Disorders in Mice.International journal of molecular sciences · 2022Article
- Long-term inorganic nitrate administration protects against ovariectomy-induced osteoporosis in rats.EXCLI journal · 2022Article
- Purinergic signaling in diabetes and metabolism.Biochemical pharmacology · 2021Review
- The Nitrate-Nitrite-Nitric Oxide Pathway on Healthy Ageing: A Review of Pre-clinical and Clinical Data on the Impact of Dietary Nitrate in the Elderly.Frontiers in aging · 2021Review
- Pharmacological Tuning of Adenosine Signal Nuances Underlying Heart Failure With Preserved Ejection Fraction.Frontiers in pharmacology · 2021Review
- Inorganic nitrate, a natural anti-obesity agent: A systematic review and meta-analysis of animal studies.EXCLI journal · 2020Review
- Dietary nitrate attenuates high-fat diet-induced obesity via mechanisms involving higher adipocyte respiration and alterations in inflammatory status.Redox biology · 2020Article
- AMP-activated protein kinase activation and NADPH oxidase inhibition by inorganic nitrate and nitrite prevent liver steatosis.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Genetic ablation of adenosine receptor A3 results in articular cartilage degeneration.Journal of molecular medicine (Berlin, Germany) · 2018Article
- Pathological overproduction: the bad side of adenosine.British journal of pharmacology · 2017Review
- Purinergic Receptors in Adipose Tissue As Potential Targets in Metabolic Disorders.Frontiers in pharmacology · 2017Review
- Nitrite-mediated reduction of macrophage NADPH oxidase activity is dependent on xanthine oxidoreductase-derived nitric oxide but independent of S-nitrosation.Redox biology · 2016Article
- Nitric oxide generation by the organic nitrate NDBP attenuates oxidative stress and angiotensin II-mediated hypertension.British journal of pharmacology · 2016Article
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8 authors at 2 institutions in 1 country.
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Abstract
rationaleAccumulating studies suggest that nitric oxide (NO) deficiency and oxidative stress are central pathological mechanisms in type 2 diabetes (T2D). Recent findings demonstrate therapeutic effects by boosting the nitrate-nitrite-NO pathway, which is an alternative pathway for NO formation. This study aimed at investigating the acute effects of inorganic nitrate on glucose and insulin signaling in adenosine A2B receptor knockout mice (A(-/-) 2B), a genetic mouse model of impaired metabolic regulation.
methodsAcute effects of nitrate treatment were investigated in aged wild-type (WT) and A(-/-) 2B mice. One hour after injection with nitrate (0.1 mmol/kg, i.p.) or placebo, metabolic regulation was evaluated by intraperitoneal glucose and insulin tolerance tests. NADPH oxidase-mediated superoxide production and AMPK phosphorylation were measured in livers obtained from non-treated or glucose-treated mice, with or without prior nitrate injection. Plasma was used to determine insulin resistance (HOMA-IR) and NO signaling.
resultsA(-/-) 2B displayed increased body weight, reduced glucose clearance, and attenuated overall insulin responses compared with age-matched WT mice. Nitrate treatment increased circulating levels of nitrate, nitrite and cGMP in the A(-/-) 2B, and improved glucose clearance. In WT mice, however, nitrate treatment did not influence glucose clearance. HOMA-IR increased following glucose injection in the A(-/-) 2B, but remained at basal levels in mice pretreated with nitrate. NADPH oxidase activity in livers from A(-/-) 2B, but not WT mice, was reduced by nitrate treatment. Livers from A(-/-) 2B displayed reduced AMPK phosphorylation compared with WT mice, and this was increased by nitrate treatment. Finally, injection with the anti-diabetic agent metformin induced similar therapeutic effects in the A(-/-) 2B as observed with nitrate.
conclusionThe A(-/-) 2B mouse is a genetic mouse model of metabolic syndrome. Acute treatment with nitrate improved the metabolic profile in it, at least partly via reduction in oxidative stress and improved AMPK signaling in the liver.
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